It is proposed to investigate the ability of a novel human endothelial cell derived protein to ameliorate adverse reactions of biomaterials in contact with blood. This protein (HEDA) has recently been purified from human endothelial cells (HUVEC) and has been found to inhibit activation of Hageman factor (factor XII) by glass. Factor XII activation can mediate the activation of coagulation, fibrinolysis, complement and kinin pathways. These pathways are important in maintaining hemostasis and controlling inflammatory reactions. The central hypothesis to be tested is that HEDA can modulate the inflammatory responses that occur when blood contacts biomaterials. To test this hypothesis, clinically relevant biomaterials will be exposed to human blood components and the quantitative effects of HEDA on activation of factor XII, prekallikrein, platelets and neutrophils, will be determined. This is a focused study, designed to assess the feasibility of regulating factor XII dependent inflammatory responses to biomaterials with a naturally-occurring inhibitor of factor XII activation. The successful conclusion of this proposal will provide information required to assess the commercial potential of HEDA, and determine if further development In a Phase II project is warranted. PROPOSED COMMERCIAL APPLICATION: Complications arising from incompatibility of blood with biomaterials is a continuing problem in the artificial organ device business. This is a $500 million a year industry in the United States alone and represents the potential commercial possibility for improved biomaterials.